"Ecstasy" is the street name of 3,4-methylenedioxymethamphetamine (MDMA), a legally controlled, recreationally used amphetamine derivative. This drug releases serotonin (5HT) and dopamine (DA) from axon terminals in the brain and, in high doses, is neurotoxic to 5HT-containing axons in laboratory animals including primates. Very little is known about how MDNM affects neuronal excitability, either acutely or after chronic, toxic exposure. These are important health related questions because of the apparently substantial use of MDMA on college campuses. One target region for MDMA-sensitive 5HT axons is the nucleus accumbens, an important nucleus in the dopaminergic reward pathway of the brain. The objectives of this proposal are to determine how acutely administered MDN4A interacts with 5HT to affect neuronal excitability in the accumbens, and to determine how chronic, neurotoxic MDMA administration alters responses of accumbens cells to 5HT, dopamine, and subsequent MDMA administration. Microiontophoresis combined with single cell recording will be used to assess how acute MDMA application alters accumbens cell excitability and to determine whether the MDMA effects are mediated by 5HT, DA or by both monoamines. In addition, effects of neurotoxic doses of MDMA on subsequent responses of accumbens cells to 5HT, DA and MDN4A will be tested. These experiments will provide insights into how MDMA affects neuronal excitability, and also will increase knowledge about how 5HT and DA act and interact to modify neurotransmission in the accumbens.